Using a selective antibody serum against glutaraldehyde-conjugated gamma-aminobutyric acid (GABA), GABAergic neurons were identified in the medial prefrontal cortex of young adult gerbils (Meriones unguiculatus) following a single non-invasive dose of methamphetamine (25 mg/kg i.p.) applied at the age of 90 days. GABA-immunoreactive profiles were electron microscopically counted in a defined test field (0.875 mm2) covering the prefrontal prelimbic area after a single dose of either methamphetamine or saline. Within 30 days following the drug challenge the density of GABAergic innervation significantly increased by about 20%. Several lines of previous investigation indicate that a single dose of methamphetamine is an appropriate stimulus to cause selective autotoxic destruction of certain prefrontal dopamine fibres due to drug-induced hyperactivation. There is further indication of postsynaptic and transneuronal neuroplasticity since the densities of dendritic spines on prefrontal pyramidal cells went through a significant sequence of post-drug gain and loss. These structural dynamics resemble typical alterations seen after classical mechanical or chemical lesioning in other regions of the brain. The present results on drug-induced reactive neuroplasticity are discussed together with the current understanding of stimulus-induced adaptive reorganization in the mammalian central nervous system.